Proximity-based differential single-cell analysis of the niche to identify stem/progenitor cell regulators
- Author(s)
- Silberstein, L; Goncalves, KA; Kharchenko, PV; Turcotte, R; Kfoury, Y; Mercier, F; Baryawno, N; Severe, N; Bachand, J; Spencer, JA; Papazian, A; Lee, D; Chitteti, BR; Srour, EF; Hoggatt, J; Tate, T; Lo Celso, C; Ono, N; Nutt, S; Heino, J; Sipila, K; Shioda, T; Osawa, M; Lin, CP; Hu, GF; Scadden, DT;
- Details
- Publication Year 2016-10-06,Volume 19,Issue #4,Page 530-543
- Journal Title
- Cell Stem Cell
- Publication Type
- Journal Article
- Abstract
- Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 27524439
- Publisher's Version
- https://doi.org/10.1016/j.stem.2016.07.004
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-08-19 02:01:12
Last Modified: 2017-08-24 11:23:13